Cellular and cytokine correlates of severe dengue infection.
BACKGROUND:The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3510251?pdf=render |
| _version_ | 1818509622271541248 |
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| author | Gathsaurie Neelika Malavige Li-Chieh Huang Maryam Salimi Laksiri Gomes S D Jayaratne Graham S Ogg |
| author_facet | Gathsaurie Neelika Malavige Li-Chieh Huang Maryam Salimi Laksiri Gomes S D Jayaratne Graham S Ogg |
| author_sort | Gathsaurie Neelika Malavige |
| collection | DOAJ |
| description | BACKGROUND:The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF. METHODOLOGY/PRINCIPAL FINDINGS:By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17. CONCLUSIONS/SIGNIFICANCE:Our data suggest that serum IL-10, TNFα and TGFβ differentially associate with dengue disease severity. |
| first_indexed | 2024-12-10T22:47:55Z |
| format | Article |
| id | doaj.art-78cff6de1dcd42e086115c057a052219 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:47:55Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-78cff6de1dcd42e086115c057a0522192022-12-22T01:30:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5038710.1371/journal.pone.0050387Cellular and cytokine correlates of severe dengue infection.Gathsaurie Neelika MalavigeLi-Chieh HuangMaryam SalimiLaksiri GomesS D JayaratneGraham S OggBACKGROUND:The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF. METHODOLOGY/PRINCIPAL FINDINGS:By using ex vivo IFNγ ELISpot assays we determined DENV-NS3 specific responses in patients with varying severity of DHF. Other cytokines produced by DENV-NS3 specific T cells were determined by using multiple bead array analysis (MBAA). We also determined the serum cytokine levels using MBAA, lymphocyte subsets and Annexin V expression of lymphocytes in patients with varying severity of DHF. Of the 112 DHF patients studied, 29 developed shock. Serum IL-10 and IP-10 levels positively and significantly correlated with T cell apoptosis while IL-10 levels inversely correlated with T cell numbers. In contrast, TGFß showed a very significant (P<0.0001) and positive correlation (Spearman's R = 0.65) with the platelet counts, consistent with platelet release. We found that whilst patients with severe dengue had lower total T cell numbers, the DV-NS3 specific T cells persisted and produced high levels of IFNγ but not TNFα, IL-3, IL-13, IL-2, IL-10 or IL-17. CONCLUSIONS/SIGNIFICANCE:Our data suggest that serum IL-10, TNFα and TGFβ differentially associate with dengue disease severity.http://europepmc.org/articles/PMC3510251?pdf=render |
| spellingShingle | Gathsaurie Neelika Malavige Li-Chieh Huang Maryam Salimi Laksiri Gomes S D Jayaratne Graham S Ogg Cellular and cytokine correlates of severe dengue infection. PLoS ONE |
| title | Cellular and cytokine correlates of severe dengue infection. |
| title_full | Cellular and cytokine correlates of severe dengue infection. |
| title_fullStr | Cellular and cytokine correlates of severe dengue infection. |
| title_full_unstemmed | Cellular and cytokine correlates of severe dengue infection. |
| title_short | Cellular and cytokine correlates of severe dengue infection. |
| title_sort | cellular and cytokine correlates of severe dengue infection |
| url | http://europepmc.org/articles/PMC3510251?pdf=render |
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